Background: Clostridium difficile infection (CDI) is a serious threat for an aging population. Using an aged mouse model, we evaluated the effect of age and the roles of innate immunity and intestinal microbiota. Methods: Aged (18 months) and young (8 weeks) mice were infected with C difficile, and disease severity, immune response, and intestinal microbiome were compared. The same experiment was repeated with intestinal microbiota exchange between aged and young mice before infection. Results: Higher mortality was observed in aged mice with weaker neutrophilic mobilization in blood and intestinal tissue and depressed proinflammatory cytokines in early infection. Microbiota exchange improved survival and early immune response in aged mice. Microbiome analysis revealed that aged mice have significant deficiencies in Bacteroidetes phylum and, specifically, Bacteroides, Alistipes, and rc4-4 genera, which were replenished by cage switching. Conclusions: Microbiota-dependent alteration in innate immune response early on during infection may explain poor outcome in aged host with CDI.
Background: Clostridium difficileinfection (CDI) is a serious threat for an aging population. Using an aged mouse model, we evaluated the effect of age and the roles of innate immunity and intestinal microbiota. Methods: Aged (18 months) and young (8 weeks) mice were infected with C difficile, and disease severity, immune response, and intestinal microbiome were compared. The same experiment was repeated with intestinal microbiota exchange between aged and young mice before infection. Results: Higher mortality was observed in aged mice with weaker neutrophilic mobilization in blood and intestinal tissue and depressed proinflammatory cytokines in early infection. Microbiota exchange improved survival and early immune response in aged mice. Microbiome analysis revealed that aged mice have significant deficiencies in Bacteroidetes phylum and, specifically, Bacteroides, Alistipes, and rc4-4 genera, which were replenished by cage switching. Conclusions: Microbiota-dependent alteration in innate immune response early on during infection may explain poor outcome in aged host with CDI.
Authors: Kevin M D'Auria; Glynis L Kolling; Gina M Donato; Cirle A Warren; Mary C Gray; Erik L Hewlett; Jason A Papin Journal: Infect Immun Date: 2013-07-29 Impact factor: 3.441
Authors: Charlie G Buffie; Vanni Bucci; Richard R Stein; Peter T McKenney; Lilan Ling; Asia Gobourne; Daniel No; Hui Liu; Melissa Kinnebrew; Agnes Viale; Eric Littmann; Marcel R M van den Brink; Robert R Jenq; Ying Taur; Chris Sander; Justin R Cross; Nora C Toussaint; Joao B Xavier; Eric G Pamer Journal: Nature Date: 2014-10-22 Impact factor: 49.962
Authors: Lisa Abernathy-Close; Michael G Dieterle; Kimberly C Vendrov; Ingrid L Bergin; Krishna Rao; Vincent B Young Journal: Infect Immun Date: 2020-05-20 Impact factor: 3.441
Authors: Pedro Henrique Q S Medeiros; Solanka E Ledwaba; David T Bolick; Natasa Giallourou; Lauren K Yum; Deiziane V S Costa; Reinaldo B Oriá; Eileen M Barry; Jonathan R Swann; Aldo Ângelo M Lima; Hervé Agaisse; Richard L Guerrant Journal: Gut Microbes Date: 2019-02-03
Authors: C Rodríguez; E Romero; L Garrido-Sanchez; G Alcaín-Martínez; R J Andrade; B Taminiau; G Daube; E García-Fuentes Journal: Gut Microbes Date: 2020-03-04
Authors: Reinaldo B Oriá; João O Malva; Patricia L Foley; Raul S Freitas; David T Bolick; Richard L Guerrant Journal: Front Hum Neurosci Date: 2018-09-19 Impact factor: 3.169